Lymphocytic alveolitis consisting predominantly of CD8 CTL is common in HIV- infected individuals and has been associated with a worse prognosis in patients with symptomatic pulmonary disease. Since one CTL function is defense against viral infections, they may be important in killing HIV- infected cells in the lung. However, this could lead to CD4 T cell and AM depletion with attendant morbidity secondary to impaired immune responses. Since CTL are active against virally infected cells, they may represent a directed local immune response against HIV infection. Accessory cells (AC), including AM, are essential for the initiation of primary immune responses as they process antigen for presentation to T cells. Once exposed to antigen and AC, T cells become activated and primed to respond in a secondary immune response upon re-exposure to antigen. Thus, AC have a critical role in regulating expansion of the CD8 CTL population. This laboratory has previously shown that AM AC function in HIV-infected patients is enhanced. This could lead to augmented CTL proliferation in the lung of these individuals. The investigators now have preliminary evidence that alveolar lymphocytes in HIV-infected patients are activated, proliferate spontaneously and in response to IL-2, and secrete a Th1 cytokine pattern (IL-2+, IFN- gamma+, IL-4, IL-10). Furthermore, this response appears to be compartmentalized within the lung.The current proposal hypothesizes that lymphocytic alveolitis in HIV-infected patients results from a local immune response to HIV infection in the lung and further contributes to the impairment of immune function by mediating depletion of CD4 positive T cells and AM. To test this hypothesis, several types of antigenic stimuli leading to CTL formation will be examined by studying the ability of different HIV-infected cells and viral strains to initiate the immune response. The ability of lung lymphocytes and AM to secrete various cytokines, especially the immunosuppressive cytokine IL- 10, will be determined. The ability to modify the Th1 and CTL response in vitro by exogenous cytokines and adhesion molecule antibodies will be determined. The capacity of lung CTL to kill virally-infected autologous CD4 T cells and AC will be assessed. The mechanisms of CTL killing will be examined. Finally, the ultimate outcome of a vigorous pulmonary CTL response will be assessed by determining if CTL killing of HIV-infected cells inactivates the virus, determining if the presence of alveolar CTL is associated with a high lung viral burden, and by determining long-term survival in asymptomatic patients with lymphocytic alveolitis. The proposed studies will give important insights into potential mechanisms of lymphocytic alveolitis in HIV-infected patients and will suggest important new mechanisms by which CD4 T cells are depleted in the lung of HIV-infected patients, thereby contributing to the immunologic defects so prevalent in these individuals.